US3769330A - 2-butyl-1-alkynyl-cycloalkan-1-ols and derivatives thereof - Google Patents

2-butyl-1-alkynyl-cycloalkan-1-ols and derivatives thereof Download PDF

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US3769330A
US3769330A US00088494A US3769330DA US3769330A US 3769330 A US3769330 A US 3769330A US 00088494 A US00088494 A US 00088494A US 3769330D A US3769330D A US 3769330DA US 3769330 A US3769330 A US 3769330A
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butyl
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acetoxy
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W Easter
E Nikawitz
R Tavares
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Givaudan Roure Corp
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Definitions

  • R' is hydrogen or methyl
  • R" is hydrogen or lower alkanoyl
  • R' is butyl
  • n is 0, 1 or 2
  • Z is a single, double, or triple bond
  • b is correspondingly 2, 1, or 0.
  • the compounds of the present invention are prepared from the corresponding Z-butylcycloalkanone by alkynylation followed, where desired by esterification and catalytic hydrogenation as shown in Chart I below.
  • theketone (I) is reacted with acetylene suitably in the form-of an alkali'metal acetylide to yield the 2-butyll-ethynyl-cycloalkan-l-ol.(II).
  • acetylene suitably in the form-of an alkali'metal acetylide to yield the 2-butyll-ethynyl-cycloalkan-l-ol.(II).
  • fmethylacetylene is reacted with ketone (1), suitably inthe'formof the 'alkynyl-Grignard reagent to yield the corresponding compound (VIII).
  • the compounds of the present invention find use as odorants and may be used in perfumes, soaps and other toilet goods.
  • the formulations may contain between 0.1% and 20% of the odorant material.
  • colognes would contain between 1 and of the odorant.
  • the reaction of the parent ketone with acetylene can be carried out using any suitable ethynylation procedure.
  • the ketones can be brought to reaction with the appropriate lithium acetylide-ethylenediamine complex, with an alkali metal acetylide in a suitable solvent, such as liquid ammonia, dimethylformamide, ether or the like at a temperature of about 0 to --50 C. or with acetylene and finely divided potassium hydroxide in methylal or similar solvents.
  • the reactants are used on an, at least, equimolecular basis; however, it is preferred to apply some excess of the acetylide and also to have an excess of acetylene present during the reaction.
  • ketones are usually added undiluted or dissolved in a solvent as for instance toluene or ether.
  • the time for addition of the ketones can vary considerably; i.e. a range of about 0.5 to about hours is appropriate; usually followed by an additional agitation period of from about miuntes to about 3 hours.
  • the ammonia is allowed to evaporate, suitably by standing under ambient temperatures for up to hours. Water, ammonium chloride solution or dilute sulfuric acidis added and the ethynyl reaction products are separated from the aqueous phase by conventional means.
  • the pertinent ketone, as such, or in a suitable solution such as tetrahydrofuran, is added during from about 15 minutes to about 3 hours followed by an additional reaction period of about 5 to 25 hours at a temperature range of about 20-40.
  • a suitable solution such as tetrahydrofuran
  • ammonium chloride solution the propynyl alcohols are extracted with a suitable water immiscible solvent and purified in the usual manner, suitably by distillation.
  • the respective vinyl and alkyl alcohols may be prepared by conventional processes.
  • the reaction of theIketones with the appropriate 'Grignard reagents, is preferred.
  • saponification of the pertinent esters leads also to the desired alcohols.
  • the parent ethynyl or propynyl. alcohols are purified by distillation at reduced pressure (about 0.1-5 mm.). They are water-white to very slightly yellowish liquids, insoluble in water but soluble in alcohols, ketones, ethers, esters and hydrocarbons. Their odor characteristic is described in the pertinent examples.
  • the esterification of the acetylenic alcohols is preferably carried out with the appropriate acid anhydrides.
  • the formates can be prepared by reaction with formic/acetic anhydride at temperatures between 0-30 for a period of 2-5 days.
  • esters higher than formic are obtained by esterification with the appropriate acid anhydride at a temperature range of about 050 for about 10-100 hours, employing catalytic amounts of phosphoric acid or any other suitable catalyst; or else the esterification can be carried out with acid anhydride at reflux (or from about 50 in the presence or absence of an alkali metal salt of the corresponding organic acid for about 2-30 hours.
  • the preferred reaction time in the foregoing reactions will vary within the times given and depends upon the nature of the reactants used. In either case, solvents like benzene, toluene, hexane or heptane may be used.
  • Other esterification methods known to those skilled in the art can be used, for example, acid chlorides with pyridine or dimethylaniline.
  • the esters are purified by distillation at reduced pressure; they are water-white to slightly yellowish colored liquids, insoluble in water but soluble in organic solvents as alcohols, ethers, ketones, esters, hydrocarbons and halohydrocarbons. Their specific odor characteristics are described in the pertinent examples.
  • the hydrogenated esters may be also obtained by reduction of the corresponding acetylenic compound.
  • the vinyl compounds are prepared by catalytic hydrogenation under pressure in the presence of Lindlar catalyst in a suitable solvent.
  • the acetylenic compound is taken up in a solvent such as hexane or the like, a 1:1 mixture of unsaturated material and solvent being suitable and hydrogenating at between 30 and 60 0., suitably at 45-50 C. at a pressure of from about 30 to about 60 p.s.i., preferably at 45-50 p.s.i. for from about 4 to 6 hours. Since the catalyst loses its catalytic ability after this time it has been found helpful to add fresh catalyst between 1 and 4 times until the calculated amount of hydrogen has been taken up.
  • the solution containing the vinyl ester (IV) is then worked up in the usual manner.
  • the fully saturated derivative (V) is most readily obtained by reduction in the presence of Raney nickel in a hydroxylic solvent under pressure. Reduction in methat about 50 p.s.i. gives desirable results.
  • the p'roduct is isolated in the usual manner.
  • the saturated product (V) can of course also be derived from the vinyl ester (IV) by hydrogenation with, say, platinum oxide or palladium on charcoal.
  • the reduced esters may be readily saponified to yield the corresponding alcohols (VI) and (VII).
  • both, the alcohols and esters of the present invention exist as cis-trans stereoisomers, whose odor characteristics differ somewhat.
  • the isomers may be separated by any known method for the resolution of hydroxyl-containing stereoisomers. It has been found that fractional distillation of the pertinent alcohols at reduced pressure leads to separation of the isomers which, in turn, can be converted to the respective stereoisomeric esters by means of previously described procedures. For the practical purpose of use in erfumery this separation is usually not necessary.
  • the compounds within the scope of the present invention include the compounds listed below. Certain of these compounds were subjected to detailed examination of their erfumery properties. For convenience these compounds are followed by a designatory letter. This letter is a reference for the subsequent tabulations.
  • i-sec-butyl-l-ethynylcyclohexanol mixtures of cis and trans
  • A 2-scc-buty1-l-ethynylcyclohexanol (cis)
  • D v C., suitably at about 25 C. and 30 to 60 p.s.i.-, suitabl- 2-n-butyl-l-ethynylcyclohexanol (cis/trans) -2-sec-butyll-ethylcycloheXanol (cis/trans) M.
  • 11:0 means a cyclopentane nucleus.
  • the numbers at the head of each column indicate the positions in said nucleus of the substituents listed in the column.
  • Cis/trans musty, minty, earthy. Cis/trans: spicy, floral, anethole. Cis/gans: iresh, minty.
  • Cis/trans woody, spicy.
  • Cis/traus warm, woody, tobacco. Cisltrans: woody, ambergris.
  • Cis/trans woody.
  • Cisltrans fresh, camphor woody. Cis/trans: musty, minty eamphoraceous; Cis/trans: weak, spicy peppery.
  • Cis/ltrans none.-
  • Cis trans camphoraceous
  • Cis/trans Cis/trans: Cis/trans: Cis/trans: Cis/trans:
  • Cis/trans Cis/trans:
  • Cis/trans spicy, caryophyllene.
  • Aroma 0hemieal 30 30' Y a0 50 10* 10 a0 a0 Benzyl iso eugenol- 27 27, V27 '27 26 27 27 27 27 Bergamot oil 291 203 271 291 286 298 298 291 291 Geranium 011 10 11 1o '10 10 11- 11 .10 .10 Lavender oil 1 32 1 33 32 32 31 33 33 32 32 Lemon 011..
  • the aroma chemicals herein evalu- 1-acetoxy-2-sec-butyl-l-ethynylcyclohexane (cis) ated can be m Perfume formulatlon? practlcal
  • the cologne without l-ac etoxya) may e use S ccess u y specl e 25 Z-sec-butyl-l-ethynylcyclohexane (cis) ,was inferior and Z-sec-butyl-l-ethynylcyclohexanol, mixture of lacking in body and strength.
  • the cologne w1thout than that without l acetoxy z sec butyl l ethylcyclohex 1-acetoxy-2-sec-butyl-l-vinylcyclohexane is inferior and not as des rable as the cologne containing 1-acetoxy-2-sec- Conclusion: but l-l-vin lc clohexane.
  • the cologne containing 2-sec-butyl-1-ethyn 1- carried out to eompareodor strengths of 2-sec-butyl-1- cyclohexanol (trans) was more appealing and of more ethynylcyclohexanol and the acetate thereof, both in cis perfume value than the cologne without 2-sec-butyl-1- and trans form to the corresponding 3-sec-butyl and 4- sec-butyl isomers; the latter being the weaker odors.
  • the following examples include those in which cyclic ketones were converted to ethynylcycloalkanols via the described processes. These reactions were analyzed by a variety of methods including infrared spectroscopy, vapor phase chromatography and nuclear magnetic resonance spectroscopy. The products were characterized by infrared spectroscopy by noting the absence of a carbonyl band in the 5.8 region (due to starting ketone) and the appearance of bands in the regions of 2.8 (broad and characteristic of alcohols), 3.0,u (sharp and characteristic of CECH) and 4.5 (sharp and characteristic of -'CEC-).
  • the NMR of the acetates is characterized by ethynyl proton resonances appearing in the range 77.3 to -r7.5. (Once again, mixtures of cis and trans isomers show distinct peaks). In addition there is a sharp singlet in the region 77.9 to 18.0 assigned to the acetoxy methyl (Cain) protons. In cases where a cis, trans mixture was run two distinct signals could be noted which, when integrated, correspond to the cis-trans ratio. Temperatures are in C., except where indicated 11: 1.
  • the benzene layer was washed three times with water. After drying withanhydrous sodium sulfateand filtration, the benzene was distilled at a pressure of 250 inm.”of mrcuryQTheie'sidual brown oil weighed 407 g. V.P'.C. analysis'indicated 25% of starting ketone and 47% of cisand 28% of tr'ans-2-sec-butyl-l-ethynylcyclohexanol.
  • the product was fractionated by means of a 37 inch column, filled with glass helices, and equipped with variable reflux take-oif. 7
  • Odor Earthy, mossy, powerful note.
  • Acetylene was passed into the agitated mixture, over a period of 30 minutes maintaining a temperature of 10.
  • 2-sec-butylcyclohexanone was added over a period of 4 hours at 10 to -5, acetylene being passed into the batch simultaneously. Agitation and injection of acetylene was continued for an additional 2 hours.
  • V.P.C. analysis (175, 20 M) indicated 47.9% cis, 22.5% trans alcohols; rest: starting ketone.
  • dilute sulfuric acid 180 g. of 93% H 80, and 351 g. of ice-water was added slowly to the cooled reaction mixture.
  • the toluene layer was separated and washed neutral with water.
  • the dried solution was freed of the solvent by distillation at reduced pressure.
  • the residual yellowish oil was dried at a pressure of 5 mm. at a temperature of 50.
  • V.P.C. analysis 20 M 42.1% starting ketone, 44.6% cis alcohol, 12.5% trans alcohol.
  • the batch was then heated to reflux and the reflux maintained by adding dropwise (very slowly) 750 ml. of H 50 while at the same time distilling out the THF.
  • the initial reaction is very exothermic, but once the active Grignard is decomposed a more rapid addition is allowed and external heating is needed to maintain reflux.
  • VPC of the crude showed 57% of the ketone unreacted. Since the ketone was diflicult to separate bydistillation, two distillations were necessary to obtain 5.1 g. of product (93% pure by VPC) 20 M.
  • n 1.4830; IR shows characteristic bands.
  • NM-R integration of ethynyl proton (CEC-H) resonances at -r7.58 and 77.51 shows a cis and trans mixture in a ratio of 7 to 1.
  • IR shows expected bands for CECH and OH and only trace carbonyl.
  • the cis and trans isomers were not resolved in VPC but NMR integration of the ethynyl proton (C CE) resonances indicated a cis and trans mixture in the ratio of 3:2. Odor: musty, minty.
  • Odor Spicy, floral, anethole.
  • the crude product was fractionated through a 24" column fitted with glass helices.
  • the fraction, going over at 53-56-at a pressure of 0.2-0.3 mm. (41.1 g.) was redistilled through a 25" spiral column: 26.9 g. of waterwhite liquid; B.P. 3 mm.: 93.94 nr 1.4713.
  • V.P.C. indicates 97.8% of isomer A (cis) and 1.6% of isomer B (trans).
  • a stream of methylacetylene was introduced over a period of 150 minutes, the batch being agitated and maintained at a temperature of 35 at the beginning and 32 atthe end. 7
  • the batch was then moderately agitated for hours at room temperature and an additional 3 hours at 50.
  • the crude product was dissolved in toluene (300 g.); the solution was quenched on ice. After standing overnight, the aqueous layer was separated in a separatory funnel. The toluene layer was washed once with a 10% sodium bicarbonate solution (200 g.) and then four times with water. It was dried with anhydrous Na SO filtered and freed of the solvent by distillation at a pressure of 60 mm. Toluene recovered (280 g.).
  • the NMR shows two ethynyl proton (--CEC H) resonances at 77.36 and 77.42 (3:1 ratio) and two methyl singlets of the acetyl group (CHaE-O) at 77.98 and 77.94 (3:1 ratio).
  • the residual oil (40.1 g.) was fractionated through a 25" spiral column.
  • the NMR had a 1 proton singlet at 77.42 assigned to the ethynyl proton (CE C I'I and a three proton singlet at 77.94 assigned to the acetoxy methyl H g-O Odor: Strong, woody, vetiveracetate ambergris.
  • Odor Sweet, musty, woody.
  • the solution was filtered from the catalyst; the solvent was distilled.
  • the residual oil weighed 65.1 g.
  • n l.4660. Odor: Woody, vetiver acetate, cedar.
  • Odor Warm, woody, tobacco, ambergris.
  • the ester had a B.P. of 8590 at a pressure of 0.4 mm, IR indicated complete esterification by lack of OH absorption.
  • reaction mixture was transferred to a separatory funnel using an additional 200 ml. of carbon tetrachloride as washes.
  • the organic layer was filtered through cotton, dried over sodium sulfate, concentrated to 500 ml. at 300 mm. pressure and used subsequently in the following synthetic step.
  • EXAMPLE XXX 1-acetoxy-2sec-butylcyclohexane A mixture of 39.0 g. 2-sec-butylcyclohexanol, 32 g. of acetic anhydride, and 0.5 g. sodium acetate was refiuxed (136 C.) for 6 hours. After cooling to C., 50 ml. of water were added and the batch refluxed an additional 30 minutes. The batch was cooled to room temperature, diluted with hexane, and the layers separated. The organic layer was washed with 2x 100 ml. water, 2x 50 ml. 5% soda ash, and then neutral with water. Distillation yielded 37.4 grams of product; B.P. 80 C. at 2 mm.
  • n l.4503. Odor: Weak, minty.
  • the mixture of cis, trans alcohols had a B.P. of 47 at a pressure of 0.8 mm.
  • R" is acetyl, propionyl or formyl.
  • a compound according to claim 1 wherein n 1, Za triple bond and R" is hydrogen.

Abstract

2-BUTYL-1-ALKYNYL-CYCLOALKAN-1-OLS AND THEIR ALKANOYL AND HYDROGENATED DERIVATIVES, ESPECIALLY THE CYCLOPENTANOL, CYCLOHEXANOL AND CYCLOHEPTANOL MEMBERS OF THIS GROUP POSSESS A STRONG, WOODY ODOR OF THE AMBERGRIS TYPE. THEIR ODORANT QUALITITES ARE ESPECIALLY VALUABLE IN PERFUMERY. THE POSITIONAL ISOMERS AND HOMOLOGOUS COMPOUNDS WITH A DIFFERENT NUMBER OF CARBON ATOMS IN THE ALKYL SIDE CHAIN DO NOT POSSESS THIS QUALITY.

Description

Un td States,
v $769,330 2-BUTYL-1-ALKYNYII-CYCLOALKAN-1-0LS AND DERIVATIVES THEREOF Edward J. Nikawitz, Glen Rck, Robert F. Tavares, Cedar Grove, and William M. Easter, Jr., Hasbrouck Heights, 5 NJ., assignors to Givaudan Corporation, Clifton, NJ. No Drawing. Filed Nov. 10, '1970, Ser. No. 88,494
Int. Cl. C07c 35/06, 35/08, 35/20 U.S. Cl. 260-488 R 12 Claims ABSTRACT OF THE DISCLOSURE Z-butyl 1 alkynyl-cycloalkanl-ols and their alkanoyl and hydrogenated derivatives, especially the cyclopentan01, cyclohexanol and cycloheptanol members of this group possess a strong, woody odor of the ambergris type. Their odorant qualities are especially valuable in perfumery. The positional isomers and homologous compounds with a different number of carbon atoms in the alkyl side chain do not possess this quality.
DESCRIPTION OF THE PRIoR ART Compounds within the scope of the present invention, are broadly disclosed as corrosion inhibitors in U .8. Pat. 2,993,864. There is no reference therein to any odorant properties of these compounds only one butyl derivative, namely 4-tert-buty1-l-ethynylcyclohexan-l-ol is disclosed. However tests described hereinbelow show that this com-v pound, as' well as its acetyl derivative have very weak odors and are totally valueless as vod orants FIELD OF THE INVENTION i f Novelcarbocyclic odorants. v
CECH RO C 2 n O 1) II 7 3,769,330 Patented Oct. 30, 19 73 SUMMARY OF THE INVENTION The compounds of the present invention possess the following general structure:
where R' is hydrogen or methyl R" is hydrogen or lower alkanoyl R' is butyl n is 0, 1 or 2; Z is a single, double, or triple bond, and b is correspondingly 2, 1, or 0.
The compounds of the present invention are prepared from the corresponding Z-butylcycloalkanone by alkynylation followed, where desired by esterification and catalytic hydrogenation as shown in Chart I below.
CHECK R"O CzHu R"O CEO-CH;
wherein n=0, 1 or R'L=lower alkanoyl, suitably formyl, acetyl, or propionyl.
In this process where the ethynyl derivatives are desired theketone (I) is reacted with acetylene suitably in the form-of an alkali'metal acetylide to yield the 2-butyll-ethynyl-cycloalkan-l-ol.(II). Where the propynyl derivative is desired fmethylacetylene is reacted with ketone (1), suitably inthe'formof the 'alkynyl-Grignard reagent to yield the corresponding compound (VIII). If desired n-butyl, (b) sec-butyl, (c) tert-butyl, (d) isoform the saturated and partially saturated derivatives compound (IH) is hydrogenated either with Lindlar catalyst to form the vinyl derivative (IV) or with Raney nickel to give the fully saturated alkyl derivative (V). Saponification of (IV) or (V) yields the appropriate alcohol (VI) or (VII). Compounds (VI) and (VII) may also be obtained directly by reaction of the ketone (I) with the appropriate vinyl or alkyl Grignard.
The compounds of the present invention find use as odorants and may be used in perfumes, soaps and other toilet goods. The formulations may contain between 0.1% and 20% of the odorant material. For example, colognes would contain between 1 and of the odorant.
However, beyond the general utility as extremely valuable perfume ingredients on account of their strong and difiusive earthy, woody, mossy, cedar, vetiver notes it is of the utmost significance that some of these compounds possess odors with a marked likeness or relationship to that of ambergris. I
It is extremely surprising and unexpected that these compounds of a relatively simple structure are endowed with this outstanding odor quality considering the rather complex chemical configurations which are associated with this important and rare type of fragrance.
Even more surprising and unexpected is the fact that compounds with a closely related chemical structure are of little or no value for perfumery on account of uninteresting, trivial, weak, even repulsive notes or because they have no odor at all.
This surprising and unexpected selectivity goes so far that the 3- and 4-position isomers of these butyl derivatives not only lack the ambergris odoriferous note but also any of the powerful valuable odor qualities inherent to the compounds of this invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS In the preferred embodiments of the invention, the reaction of the parent ketone with acetylene can be carried out using any suitable ethynylation procedure. For example, the ketones can be brought to reaction with the appropriate lithium acetylide-ethylenediamine complex, with an alkali metal acetylide in a suitable solvent, such as liquid ammonia, dimethylformamide, ether or the like at a temperature of about 0 to --50 C. or with acetylene and finely divided potassium hydroxide in methylal or similar solvents.
The specific procedures utilized are well known in the ethynylation art, however, yields are optimized if certain specific procedures are followed.
To insure complete reaction of the metal acetylide with the ketones the reactants are used on an, at least, equimolecular basis; however, it is preferred to apply some excess of the acetylide and also to have an excess of acetylene present during the reaction.
The ketones are usually added undiluted or dissolved in a solvent as for instance toluene or ether.
The time for addition of the ketones can vary considerably; i.e. a range of about 0.5 to about hours is appropriate; usually followed by an additional agitation period of from about miuntes to about 3 hours. The ammonia is allowed to evaporate, suitably by standing under ambient temperatures for up to hours. Water, ammonium chloride solution or dilute sulfuric acidis added and the ethynyl reaction products are separated from the aqueous phase by conventional means.
For the preparation of the propynyl alcohols reaction with the Grignard compound of methylacetylene is preferred, i.e. with According to conventional methods a Grignard solu: tion is prepared from magnesium and bromoethane in a suitable solvent, such as tetrahydrofurani Methylacetylene is introduced over a period of about one to three hours at a temperature range of about 20-40.
The pertinent ketone, as such, or in a suitable solution such as tetrahydrofuran, is added during from about 15 minutes to about 3 hours followed by an additional reaction period of about 5 to 25 hours at a temperature range of about 20-40. After addition of ammonium chloride solution the propynyl alcohols are extracted with a suitable water immiscible solvent and purified in the usual manner, suitably by distillation.
Stoichiometric quantities of the pertinent reactants (Grignard, ketone) are usually utilized although an excess of about up to 20% of either one does not impair the proper progress of the reaction.
The respective vinyl and alkyl alcohols may be prepared by conventional processes. The reaction of theIketones with the appropriate 'Grignard reagents, is preferred. The choice of solvents, temperature ranges, stoichiometric amounts and their variations etc., would be apparent to those skilled in the art. As mentioned, saponification of the pertinent esters leads also to the desired alcohols. The parent ethynyl or propynyl. alcohols are purified by distillation at reduced pressure (about 0.1-5 mm.). They are water-white to very slightly yellowish liquids, insoluble in water but soluble in alcohols, ketones, ethers, esters and hydrocarbons. Their odor characteristic is described in the pertinent examples. v e
The corresponding vinyl and, saturated alcohols are also purified by distillation as described above. Their appearance and solubility conform to that of their triply bonded congeners.
The esterification of the acetylenic alcohols is preferably carried out with the appropriate acid anhydrides. For instance, the formates can be prepared by reaction with formic/acetic anhydride at temperatures between 0-30 for a period of 2-5 days.
The esters higher than formic are obtained by esterification with the appropriate acid anhydride at a temperature range of about 050 for about 10-100 hours, employing catalytic amounts of phosphoric acid or any other suitable catalyst; or else the esterification can be carried out with acid anhydride at reflux (or from about 50 in the presence or absence of an alkali metal salt of the corresponding organic acid for about 2-30 hours.
The preferred reaction time in the foregoing reactions will vary within the times given and depends upon the nature of the reactants used. In either case, solvents like benzene, toluene, hexane or heptane may be used. Other esterification methods known to those skilled in the art can be used, for example, acid chlorides with pyridine or dimethylaniline. The esters are purified by distillation at reduced pressure; they are water-white to slightly yellowish colored liquids, insoluble in water but soluble in organic solvents as alcohols, ethers, ketones, esters, hydrocarbons and halohydrocarbons. Their specific odor characteristics are described in the pertinent examples.
The hydrogenated esters may be also obtained by reduction of the corresponding acetylenic compound. The vinyl compounds are prepared by catalytic hydrogenation under pressure in the presence of Lindlar catalyst in a suitable solvent. Suitably, the acetylenic compound is taken up in a solvent such as hexane or the like, a 1:1 mixture of unsaturated material and solvent being suitable and hydrogenating at between 30 and 60 0., suitably at 45-50 C. at a pressure of from about 30 to about 60 p.s.i., preferably at 45-50 p.s.i. for from about 4 to 6 hours. Since the catalyst loses its catalytic ability after this time it has been found helpful to add fresh catalyst between 1 and 4 times until the calculated amount of hydrogen has been taken up. The solution containing the vinyl ester (IV) is then worked up in the usual manner.
The fully saturated derivative (V) is most readily obtained by reduction in the presence of Raney nickel in a hydroxylic solvent under pressure. Reduction in methat about 50 p.s.i. gives desirable results. The p'roductis isolated in the usual manner. The saturated product (V) can of course also be derived from the vinyl ester (IV) by hydrogenation with, say, platinum oxide or palladium on charcoal.
The reduced esters may be readily saponified to yield the corresponding alcohols (VI) and (VII).
It should be noted that both, the alcohols and esters of the present invention, exist as cis-trans stereoisomers, whose odor characteristics differ somewhat. The isomers may be separated by any known method for the resolution of hydroxyl-containing stereoisomers. It has been found that fractional distillation of the pertinent alcohols at reduced pressure leads to separation of the isomers which, in turn, can be converted to the respective stereoisomeric esters by means of previously described procedures. For the practical purpose of use in erfumery this separation is usually not necessary.
The compounds within the scope of the present invention include the compounds listed below. Certain of these compounds were subjected to detailed examination of their erfumery properties. For convenience these compounds are followed by a designatory letter. This letter is a reference for the subsequent tabulations.
i-sec-butyl-l-ethynylcyclohexanol, mixtures of cis and trans (A) 2-scc-buty1-l-ethynylcyclohexanol (cis) (D) v C., suitably at about 25 C. and 30 to 60 p.s.i.-, suitabl- 2-n-butyl-l-ethynylcyclohexanol (cis/trans) -2-sec-butyll-ethylcycloheXanol (cis/trans) M. U v2rs se uty -lr cy l h eaq (si tr 2 -sec-bu tyl-1- l-propynyl) -cyclohexanol (cis/ trans) 1-acetoxy-2 sec-butyl-l-ethynylcyclohexane, mixture of cis and trans..(B) l-acetoxy-Z -sec-bhtyl-l-ethynylcyclohexane (cis) (F) l-acetoxy-Z-sec-butyl-l-ethynylcyclohexane (trans) (G) Z-sec-butyl-l-ethynyl-l-formyloxycyclohexane (cis/trans) (H) Z-sec-butyl-I-ethynyl-1-propiony1oxycyclohexane (cis/trans) 1-acetoxy-2-sec-butyl-vinylcyclohexane (cis/trans) (C) l-acetoxy-2-sec-butyl-l-ethynylcyclopentane (cis/trans) 1-acetoxy-2-tert-butyl-l-ethynylcyclohexane (cis/ trans). 2-tert-butyl-l-ethynylcyclohexanol (cis/trans) 1-acetoxy-2-sec-butyl-l-ethynylcycloheptane (cis/trans) 1-acetoxy-2-iso-butyl-l-ethynylcyclohexane (cis/trans) l-acetoxy-2-n-butyl-ethynylcyclohexane (cis/trans) l-acetoxy-Z-sec-butyl-l-ethylcyclohexane (cis/trans) (I) l-acetoxy-Z-sec-butybl-( l-propynyl) -cyclohexane (cis/trans) The odorant quality of the compounds of the present invention and certain other compounds of related structure are summarized below. In accordance with the typical structure of Compounds II and III above in the following table n=1 means a cyclohexane nucleus, n=2 means a cycloheptane nucleus and 11:0 means a cyclopentane nucleus. The numbers at the head of each column indicate the positions in said nucleus of the substituents listed in the column.
C CE sec-Bu C CE sec-Bu CECE sec-Bu C E CE n-Bu Ethyl sec-Bu Vinyl sec-Bu CECC sec-Bu CECE sec-Bu C E CE sec-Bu C CE sec-B11 C CE sec-Bu CECE sec-Bu CECE tort-Bu Vinyl sec-Bu C CH n-Bu C CE iso-Bu Ethyl sec-Bu -O C-O sec-Bu C E OH I tort-Bu C CE lso-Bu CECE sec-Bu CECE sec-Bu sec-Bu C CE cyclohexyl CECE iso-propyl C E CH C E CH CHQCOO C CE O C E CH 'n=0 i 0 C CE sec-Bu CHaCOO C CE sec-Bu n=2- 7 HO C CE see-Bu CH COO C CE sec-Bu cis/trans: powerful, earthy, mossy; Cis: musty, fresh earthy.
Trans: musty, minty, earthy. Cis/trans: spicy, floral, anethole. Cis/gans: iresh, minty.
o. Cis/trans: woody, spicy.
Cis/traus: warm, woody, tobacco. Cisltrans: woody, ambergris.
Cis/trans: woody.
Cisltrans: fresh, camphor woody. Cis/trans: musty, minty eamphoraceous; Cis/trans: weak, spicy peppery.
cis/trans: weak, minty.
Cis/ltrans: none.-
Cis trans: camphoraceous;
weak, oily.
weak, ethereal.
weak, woody, trace peppery. weak, floral.
Cis/trans: Cis/trans: Cis/trans: Cis/trans:
Cis/trans: Cis/trans:
Cis/trans: spicy, caryophyllene.
strong, earthy. woody, vetiver acetate cedar.
Nora. Bu butyI.
2-sec-butyl-l-ethynylcyclohexanol (trans) (E) Z-sec-butyl-l-ethynylcyclopentanol: (cis/ trans) 2-sec-butyl-l-ethynylcycloheptanol;(cis/trans) 2-iso-butyl-l-ethynylcyclohexanol (cis/trans) Cis/trans: warm, woody, cedar.
the cologne with and without the aroma chemical.
m tes-001 5155 V v I a B .C D, E a .11V .1
Aroma 0hemieal 30 30' Y a0 50 10* 10 a0 a0 Benzyl iso eugenol- 27 27, V27 '27 26 27 27 27 27 Bergamot oil 291 203 271 291 286 298 298 291 291 Geranium 011 10 11 1o '10 10 11- 11 .10 .10 Lavender oil 1 32 1 33 32 32 31 33 33 32 32 Lemon 011.. 273 275 273 273 205 275 275 273 273 Lime oil..; 54 55 54 54 53 55 55 54 54 Neroli o1l 10 11 10 10 10 11 11- 1O 10 Orange bitter- 140 14.2; 140 140 138 143 143 140 140 Orange sweet 75 77 75 75 74 77 77 75 75 Rosemary 011 32 a3 a2- 32 a1 33 as 32 32 Sage clary oil 21 22 21 21 21 22 22 21 21 Thyme oil (White). 5 5 5 5 5 5 5 5 5 Total 1.000 1.000 1. 000 1. 000 1.000 1. 000 1.000 1. 000 1. 000
For the most part, the aroma chemicals herein evalu- 1-acetoxy-2-sec-butyl-l-ethynylcyclohexane (cis) ated can be m Perfume formulatlon? practlcal The pure cis isomer of l-acetoxy-Z-sec-butyl-l-ethynylrange extending from 01% to This W111 vary of 20 clohexane has a strong woody, amber odor. The addition course, depending upon the type of fragrance formula of 1% of 1 acetoxy z sec butyl bethynylcyclohexane involved. In the above cologne, the best results were ob- 1s) to the cologne formula produced a very pleaslng tamed when the arpma chemlcals W used m the range woody note and contributed a considerable amount of 3 gg to 5 Z i g fi ggi lg 233 strength to the fragrance. The cologne without l-ac etoxya) may e use S ccess u y specl e 25 Z-sec-butyl-l-ethynylcyclohexane (cis) ,was inferior and Z-sec-butyl-l-ethynylcyclohexanol, mixture of lacking in body and strength.
61S and trans 1-aeetoxy-2-sec-buty1-l-ethynyleyclohexane (trans) This mixture of cis and trans alcohol has a very mossy- Th e pure trans isomer of 1-acetoxy-2-sec-butyl-l-ethyearthy odor The addmon of 3% 2'sec'butyl'l'ethynylnylcyclohexane, has a strong, rich woody odor. The addicyclohexanol to test cologne glves a Soft t note tion of 1% of l-acetoxy-Z-sec-butyl-l-ethynylcyclohex- :3 the fragrance an unfusual fi g i ane (trans) to the cologne formula produced a rich woody e co ogne Supenor per It Out H Y character which gave a much more desirable product ethynylcyclohexanol the cologne did not have the unlque than the Cologne without l acetoxy z sec butyl bethynyb freshness and strength. cyclohexane (trans).
l-acetoxy-Z-sec-butyl-1 -ethynylcyclohexane, mixture 2 Sec buty1 1 ethyny1 l formyloxycyclohexane of cis and trans (cis/trans) This mixturedof g fi zflceglte a g This mixture of cis-trans formates has a woody-amber woody amber o e a 0 1 a o 40 odor but is a little weaker than the acetate. The addition sfac'butyl'l'ethynylcyclohexane to the test cqlogne adds a of 3% of Z-sec-butyl-l-ethynylrl-formyloxycyclohexane W woody character The cologne Without to the cologne formula, produced a pleasing warm woody pleasing. The r1chness and balance contributed by 1- effect The cologne containing 2 sec buty1 1 ethyny1 1 oxy'zsec'butyl'l'ethynylcyclc'hexane 1S i i not a formyloxycyclohexane (cis/trans) was considered of more aetXy 2'sec'butyl"l'ethynylcyclohexane m thls case perfume value than that without 2-sec-butyl-l-ethynyl-1 outstandmg' formyloxycyclohexane (cis/trans). r
1-acetoxy-2-sec-butyl-l-vinylcyclohexane (cis/trans) l acetoxy z sec butyl bethylcyclohexafie (cis/trans) This mixture 9 the cis and trans acetate has a woody This mixture of acetate has a woodyamber odor. The ambm' odor but 15 not as lacetoxy'z'sec'butyl' addition of 3% of 1-acetoxy-2-sec-butyl-l-ethylcyclohexl-ethynylcyclohexane. The addition of 3% of l-acetoxyane to the test cologne Produced a pleasing warmwoody z'sec'butyll'vmylcyclohexane to the adds effect. The cologne containing l-acetoxy-Z-sec-butyl-l-ethwarm woody note to the fragrance and contributes to the ylcyclohexane was considered of more perfume value overall balance of the fragrance. The cologne w1thout than that without l acetoxy z sec butyl l ethylcyclohex 1-acetoxy-2-sec-butyl-l-vinylcyclohexane is inferior and not as des rable as the cologne containing 1-acetoxy-2-sec- Conclusion: but l-l-vin lc clohexane.
y y y The esters of the various der1vat1ves of 2-sec-buty1-1- z'sec'butyl'l'ethynylcyclohexanol ethynylcyclohexanol for the most part have woody-amber The pure cis isomer of 2-sec-butyl-l-ethynylcyclohexa- OdPYSWhiCh Perform wnslstemly W611 111 p g m 1 h a very f h earthy d The i i of 3% of lations. Deslrable effects are produced wh1ch mclude this material to the cologne gives a very refreshing green .1 addefl Strength and h- Moreover, these ester? 111 earthy effect. The cologne with 2-sec-butyl-1-ethynylcyy have the ablhty to contrlbute modlficaclohexanol cis is more pleasing and is preferred over that U011 wh1ch Improves the Overall balance of the P without 2-sec-buty1-l-ethynylcyclohexanol (cis). The most useful of these, fY- Y Y Y cyclohexane (cis and trans) (B) 1s an outstanding aroma 2-sec-butyl-l-ethynylcyclohexanol (trans) chemical in all respects The pure trans isomer of 2-sec-butyl-l-ethynylcyclo- Z-sec-butyl-l-ethynylcyclohexauol, (A), is a desirable hexanol has an earthy-minty odor. The addition of 5% of aroma chemical in its own right and can be used extentrans-Z-sec-butyl-l-ethynylcyclohexanol to the cologne sively in many types of fragrances in which it will conformulation gave a freshness which tended to be more tribute the fresh earthiness demonstrated above. minty in effect than the cis isomer, Z-sec-butyl-l-ethynylcy- Specific comparison of odor strengths.-Tests were clohexanol. The cologne containing 2-sec-butyl-1-ethyn 1- carried out to eompareodor strengths of 2-sec-butyl-1- cyclohexanol (trans) was more appealing and of more ethynylcyclohexanol and the acetate thereof, both in cis perfume value than the cologne without 2-sec-butyl-1- and trans form to the corresponding 3-sec-butyl and 4- sec-butyl isomers; the latter being the weaker odors. In
ethvnylcyclohexanol (trans);
Cis-Z-sec-butyl-l-ethyny1cyelohexanol }4Xcis/trans 4 sec butyl- Trans-2-see-butyl-l-ethynylcyclohexanoll-ethynylcyclohexanol. Ole/trans 2 sec butyl 1 ethynylcyclo- 2Xcis/trans -3 see -butylhexanol. l-ethynylcyclohexanol. 1 actitrfixy cis 2 sec butyl 1 ethynyleye exane. 1 acetoxy trans -2 sec -butyl 1 ethynylgi g f i gig? cyclohexane' ethynylcyclohexane. 1 acetoxy cis/trans 2 sec butyl 1 ethynylcyclohexane.
The following examples include those in which cyclic ketones were converted to ethynylcycloalkanols via the described processes. These reactions were analyzed by a variety of methods including infrared spectroscopy, vapor phase chromatography and nuclear magnetic resonance spectroscopy. The products were characterized by infrared spectroscopy by noting the absence of a carbonyl band in the 5.8 region (due to starting ketone) and the appearance of bands in the regions of 2.8 (broad and characteristic of alcohols), 3.0,u (sharp and characteristic of CECH) and 4.5 (sharp and characteristic of -'CEC-).
The compounds were analyzed by vapor phase chromatography which, in most cases, gave distinct and separate peaks for the starting ketone, the cis and the trans k-alkyl- I-ethynylcycloalkanols (k=2, 3, 4).
Complementary to vapor phase chromatography was nuclear magnetic resonance spectroscopy. In the cases studied the chemical shift of the ethynyl proton of the cis isomer diifered from that of the trans. The NMR of cis/ trans mixtures revealed two sharp singlets in the region 'r7.4+7.6 which were separated by anywhere from 0.3 to 0.5 Units. These were assigned to the ethynyl protons (CECE) of the two isomers. The ratio of these two signals, when integrated, correspond to the ratio of cisztrans isomers as obtained by vapor phase chromatography.
In a similar manner the corresponding acetates derived from the ethynylcycloalkanols were characterized in the infrared by the absence of the 2.8 1. band (characteristic of the starting alcohols) and the appearance of an ester carbonyl at 5.8,. The bands at 3.0 and 4.5,u due to the acetylene moiety remain.
The NMR of the acetates is characterized by ethynyl proton resonances appearing in the range 77.3 to -r7.5. (Once again, mixtures of cis and trans isomers show distinct peaks). In addition there is a sharp singlet in the region 77.9 to 18.0 assigned to the acetoxy methyl (Cain) protons. In cases where a cis, trans mixture was run two distinct signals could be noted which, when integrated, correspond to the cis-trans ratio. Temperatures are in C., except where indicated 11: 1.
. EXAMPLE I 2-sec-butyl-l-ethynylcyclohexanol (cis, trans) (IIb) Lithium acetylide ethylenediamine complex (255 g.) and dry benzene (2040 ml.) were charged into a 5 l. flask fitted with a sealed stirrer, a thermometer, a dropping funnel, a gas inlet tube (not dipping into the liquid) and a reflux condenser with drying tube. Dry nitrogen was introduced throughout the reaction.
Z-sec-butylcyclohexanone (393 g.) was added at 40 over a period of one hour to the agitated suspension. Agitation was then continued for 6 hours at 43-45".
After cooling to water (1200 ml.) was added over a period of 30 minutes. Agitation was continued for 18 hours.
The benzene layer was washed three times with water. After drying withanhydrous sodium sulfateand filtration, the benzene was distilled at a pressure of 250 inm."of mrcuryQTheie'sidual brown oil weighed 407 g. V.P'.C. analysis'indicated 25% of starting ketone and 47% of cisand 28% of tr'ans-2-sec-butyl-l-ethynylcyclohexanol.
The product was fractionated by means of a 37 inch column, filled with glass helices, and equipped with variable reflux take-oif. 7
After removal of fractions, containing mostly starting ketone and intermediary fractions of ketone and mostly cis-product, a blend of cisand trans was collected, distilling at 56 60 at a pressure of 0.2-0.1 mm. Yield: 198.4 g.; V.P.C. 56.5% cis, 42.4% trans; Water-white liquid.
Analysis for C H O (percent): Calcd. C, 79.94; H, 11.18. Found C, 79.78; H, 11.18.
Odor: Earthy, mossy, powerful note.
EXAMPLE II Z-sec-butyl-l-ethynylcyclohexanol (cis, trans) (IIb) Powdered potassium hydroxide (112 g.) and methylal (230 g.) were charged into a 1 l. flask fitted with a sealed stirrer, a thermometer, a gas inlet tube and 'a reflux condenser.
Acetylene was passed into the agitated mixture, over a period of 30 minutes maintaining a temperature of 10.
2-sec-butylcyclohexanone was added over a period of 4 hours at 10 to -5, acetylene being passed into the batch simultaneously. Agitation and injection of acetylene was continued for an additional 2 hours.
Water (500 ml.) was added to the cooled reaction mixture. An oily layer separated. The aqueous layer was extracted with toluene (200 ml.). The extract was combined with the oily layer. The solvent was distilled at reduced pressure. The residual oil weighed 86.5 g. after drying at a pressure of 5 mm. at a temperature of 50.
V.P.C. analysis (175, 20 M) indicated 47.9% cis, 22.5% trans alcohols; rest: starting ketone.
EXAMPLE III 2-sec-butyl-l-ethynylcyclohexanol (cis, trans) (IIb) Liquid ammonia (500 ml.) was charged into a 2 1. insulated flask fitted with a sealed stirrer, a thermometer, a gas inlet tube and a Dry Ice condenser. Acetylene was passed into the ammonia for a period of 5 minutes. Sodium (25 g.) was dissolved into the ammonia by gradual addition during 45 minutes, the acetylene stream being continued.
2-sec-butylcyclohexanone g.) in dry toluene (100 ml.) was added over a period of 3 hours, continuing the acetylene stream.
Agitation was continued for 2 /2 hours. The acetylene was passed in at a somewhat slower rate.
The part of the ammonia which had evaporated was replaced by an equal volume of liquid ammonia. After standing overnight, most of the ammonia was evaporated by inserting the flask in a warm Water-bath. As the batch temperature reached 0, a solution of 58 g. of ammonium chloride in 300 ml. of water was added slowly, the flask being cooled in an ice-methanol bath.
Then, dilute sulfuric acid (180 g. of 93% H 80, and 351 g. of ice-water) was added slowly to the cooled reaction mixture.
The toluene layer was separated and washed neutral with water. The dried solution was freed of the solvent by distillation at reduced pressure. The residual yellowish oil was dried at a pressure of 5 mm. at a temperature of 50.
Yield: 167 g.
V.P.C. analysis 20 M): 42.1% starting ketone, 44.6% cis alcohol, 12.5% trans alcohol.
1 1 "EXAMPLE IV Z-sec-butyll-ethynylcyclohexanol (cis), (IIb, 1
EXAMPLE V 2-sec-butyl-l-ethynylcyclohexanol (trans) (IIb, 111:1)
This compound was obtained in accordance with the procedure of Example IV; B.P. 52-54/0.08 mm.; NMR: (CDCl )v-7.56 (CEQE) water-white liquid; n 1.4824. Odor: Musty, minty earthy.
EXAMPLE VI 2-sec.-butyl cyclopentanone (Ib, n-=) A mixture of cyclopentanone (1 mole), 99 g. (1 mole) of cyclohexylamine and 300 ml. of benzene were refluxed until the theoretical amount of water (18 ml.) was separated in a Dean and Stark tube. The residue is cyclopentylidene cyclohexylamine.
To 473 ml. (1.35 mole) of a 2.9 molar solution of methyl magnesium chloride refluxing under a blanket of dry nitrogen was added 231.4 g. (1.4 mole) of cyclopentylidene cyclohexylamine at a rate which was determined by the rate of gas evolution (methane) as measured by a gas meter. The mixture was refluxed an additional 15 min. before adding 205 g. (1.5 mole) of 2- bromobutane dropwise over a 2 hour period. After diluting with 200 ml. of tetrahydrofuran the reaction was stirred an additional 16 hours at 65-70 during which a solid precipitate formed.
The batch was then heated to reflux and the reflux maintained by adding dropwise (very slowly) 750 ml. of H 50 while at the same time distilling out the THF. The initial reaction is very exothermic, but once the active Grignard is decomposed a more rapid addition is allowed and external heating is needed to maintain reflux.
The crude oil was isolated via cohobation as it was formed during the hydrolysis. Distillation gave 68.7 g. (35.8% of theory) of Z-sec-butyl cyclopentanone as a colorless liquid, B.P. (7 mm.) =68 C., n =1.4494.
EXAMPLE VII 2-sec-buty1-l-ethynylcyclopentanol (IIb, n=0) To a mixture of 48 g. of lithium acetylide ethylenediamine complex in 120 ml. toluene and 120 ml. tetrahydrofuran was added 53 g. of Z-sec-butylcyclopentanone in the manner described in Example I.
After 120 ml. water had been added to decompose the lithium salts, 200 ml. ether was added to aid sep aration and the organic layer was washed with 100 g. H O. The organic layer was a thick emulsion and was washed with 10% HCl to break it up. It was then washed neutral with water, concentrated to an oil and distilled on a 9" column packed with glass helices. Separation was diflicult but 8.5 g. of pure ethynyl alcohol, B.P. 93 at 8 mm., n 1.4772 was obtained. The IR showed no carbonyl and did show the characteristic bands for CECH and -OH.
Integration of the ethynyl proton (CECE) resonances at -r7.43 and 7749 indicated a cisztrans ratio of 3:2. Odor: Strong, earthy.
EXAMPLE VIII 2-sec-butyl-cycloheptanone (1b, n =2) In accordance with the procedure of Example VI, but
using 0.7 molar quantities and using cycloheptanone in place of cyclopentanone there was obtained cycloheptyli denecyclohexylamine, which was. further'reacted in accordance with the procedure of Example VI, with the exception that 10% H Cl was used, for the *hydrolysis step-After 4-hours refluxin the aqueous HCl it was found that the bulk of the material could not be extracted with ether. The batch was then neutralized with solid soda ash, made basic with 10% NaOH and extracted with methylene chloride. After washing neutral, concentrating to an oil and distillation there was obtained N-(Z-sec-butyl)cycloheptylidene cyclohexylamine 75.0 g. (43% theory) a yellowish oil, B.P. (3.0 mm.)=1.43 C.j n -=1.4930. p
Analysis.Calcd. for C H N (percent): C, 81.85; H,- 12.53; N, 5.62. Found (percent): C,81.42; H, 12.38; N, 5.56. I
63.2 g. N (2 sec-butyl)cycloheptylidene cyclohexylamine (.25 mole) in 500 ml. of 20% H was refluxed for hours during which time 29.8 g (71% theory) of crude 2-sec-butyl-cycloheptanone was recovered by cohobation. Distillation gave a colorless oil, B.P. (1.5 mm.)=76 C.; n =l.4641.
EXAMPLE Ix 2-sec-butyl-l-ethynylcycloheptanol (IIb) (11:2)
20 g. of lithium acetylide ethylenediamine complex in 100 ml. toluene was reacted with 30 g. Z-sec-butyl-cyclo heptanone in accordance with the procedure as described in Example I.
VPC of the crude showed 57% of the ketone unreacted. Since the ketone was diflicult to separate bydistillation, two distillations were necessary to obtain 5.1 g. of product (93% pure by VPC) 20 M.
n 1.4830; IR shows characteristic bands. NM-R integration of ethynyl proton (CEC-H) resonances at -r7.58 and 77.51 shows a cis and trans mixture in a ratio of 7 to 1.
Odor: Spicy, caryophyllene.
EXAMPLE X 2-iso-butyl-1-ethynylcyclohexanol (IId) 7.0 g. of 2-iso-butylcyclohexanone was reacted with 5 g. of lithium acetylide ethylenediamine complex in 12 ml. toluene and 12 ml. tetrahydrofuran as described in Example I.
Distillation on a short path micro still afforded 0.8 g. of 94.5% pure (VPC, 20 M) of ethynyl alcohol, B.P. 64-64.5 at 0.5 mm.; 11 1.4740.
IR shows expected bands for CECH and OH and only trace carbonyl. The cis and trans isomers were not resolved in VPC but NMR integration of the ethynyl proton (C CE) resonances indicated a cis and trans mixture in the ratio of 3:2. Odor: musty, minty.
EXAMPLE XI 2-n-butyl-l-ethynylcyclohexanol (Ha) 7.0 g. (.045 'mole) of 2-n-butylcyclohexanone was reacted with 5 g. (.05 mole) of lithium acetylide ethylene diamine complex in 12 ml. toluene and 12 ml. tetrahydrofuran as described in Example I.
Distillation in a short path micro still afforded 1.5 g. of ethynyl alcohol (97.5% pure by VPC). B.P. 78 C. at 0.5 mm. n 1.4758. IR shows characteristic bands for CECH and OH and only trace of carbonyl. The-cis and trans isomers were not resolved in VPC but NMR integration of the ethynyl proton (CEO-g) resonances indicated a cis and trans mixture in the ratio of 3:2.
Odor: Spicy, floral, anethole.
EXAMPLE XII 2-sec-buty1-l-ethylcyclohexanol (VIIb) A Grignard solution was prepared from magnesium (12.2 g.), ethyl bromide (55 g.) and ethyl ether (325 ml.) in a l l. flask fitted with a sealed stirrer, a thermometer, a refl'ux condenser (drying tube) and a dropping funnel. v
I'2-sec-butylcyclohexanone (77 g.) in ethyl ether (100 ml.) was added to the agitated Grignard solution over a period of 45 minutes maintaining slight reflux. After refluxing an additional hours and standing overnight, ammonium chloride solution-was added .The ethereal solution was washed with water, dried and filtered. The ether was distilled. Yield of the residual oil: 81.5 g. V.P.C. about 35% of starting ketone, about 61% of 2- sec-butyl-l-ethylcyclohexanol (58% isomers A, 3% isomer B).
The crude product was fractionated through a 24" column fitted with glass helices. The fraction, going over at 53-56-at a pressure of 0.2-0.3 mm. (41.1 g.) was redistilled through a 25" spiral column: 26.9 g. of waterwhite liquid; B.P. 3 mm.: 93.94 nr 1.4713.
Odor: fresh minty.
IR indicates OH (strong) and a trace of C0.
V.P.C. indicates 97.8% of isomer A (cis) and 1.6% of isomer B (trans).
EXAMPLE XIII 2-sec.-butyll-vinylcyclohexanol (VIb l-acetoxy-Z-sec-butyl 1 vinylcyclohexane (8.9 g.), alcohol (50 ml.) and a solution of sodium hydroxide (4 g.) in water (5 ml.) were agitated and refluxed for 4 hours.
The solution was freed of solvent by distillation at reduced pressure. 'Ice-water (100 ml.) was added and the mixture was acidified with dilute sulfuric acid. The organic layer was extracted with hexane (50 ml.); the extract was washed with water and dried with anhydrous sodium sulfate. After filtration, the hexane was distilled at reduced pressure. The residual oil (7.1 g.) was distilled at a pressure of 0.08 mm. The desired alcohol (5.1 g.) had.a B.P..0f50-56.
IR: Compatible. 11, 1.4817. Odor: fresh minty.
' 1 EXAMPLE XIV 2-sec-butyl-1-(l-propynyl) cyclohexanol (VIIIb) A Grignard solution was prepared from magnesium (14.5 g.) and bromoethane (72 g.) in tetrahydrofuran (400 ml.). The preparation was carried out under nitrogen at a temperature not exceeding 38".
A stream of methylacetylene was introduced over a period of 150 minutes, the batch being agitated and maintained at a temperature of 35 at the beginning and 32 atthe end. 7
, 2 -.sec-butylcyclohexanone (77 g.) was addtd at over a period of 30 minutes. After agitation for 15 hours (under nitrogen) at room temperature, the temperature was raised to for 4 hours. Ammonium chloride solution was added and the alcohol was extracted .with toluene. f The crude product (97.3 g.) was obtaintd as residue after distillation of the toluene at reduced pressure. V.P.C. analysis indicated 1.9% toluene, 3.97% starting ketone, 72.4% cis alcohol andfl2l.4%v trans alcohol.
Fractionation through a 2 f t. column (fitted with glass helices) furnished the pure product, boiling at 88-90 at a pressure of 1 mm. It contained 72.6% of the cis isomer and 27.4% of the trans isomer.
OdorrGreen, woody, ambergris.
. EXAMPLE XV l-acetoxy 2-sec-butyl:1-ethynylcyclohexane (IIIb)? 2-sec-butyl-l-ethynylcyclohexanol (142.3 g., 56.5% cis, 42.4% trans) and acetic, anhydride (400 ml.) were agitatedand refluxed (temperature of batch: 143) in a suitable vessel for 3 hours. After cooling to the batch was quenched on ice. The acetic acid was neutralized with sodium bicarbonate. The organic layer was taken up in hexane and washed several times with water. After drying with anhydrous sodium sulfate and filtration, the hexane was distilltd at a pressure of 250 mm. The residual yellowish oil weighed 161 g. It was fractionated by means of a 37 inch column fitted with glass helices and equipped with variable reflux take-01f.
After removal of fractions containing starting material and a blend of starting material and ester (monitored by IR analysis), the pure desired compound distilled at 84.5-86 at a pressure of 1.2-0.9 mm.
Yield: 95.3 g.; water-white liquid.
Calcd. Found Analysis for O HzzOz:
Percent 0---- 75. 63 74. 86 Percent 11.... 9. 97 10. 03 A.V 0 0 S.V 252 254 at I and 77-9 EXAMPLE XVI 1-acetoxy-2-sec-butyl-l-ethynylcyclohexane Z-sec-butyl-l-ethynylcyclohexanol, obtained by ethynylation of Z-sec-butylcyclohexanone with acetylene in liquid ammonia in the presence of sodium acetylide, (119.5 g.), consisting of 12-14% of 2-sec-butylcyclohexanone, 65-68% of cisand 20% of trans-alcohol was placed into a 250 ml. flask fitted with a sealed stirrer, a reflux condenser with drying tube, a thermometer and a dropping funnel.
A mixture of acetic anhydride (84 g.) and phosphoric acid (1 g.) was added to the agitated charge according to the following schedule.
About .half of the acetylating agent was added over a period of 10 minutes. The temperature rose from 26 to 30. After a pause of 6 minutes, addition was resumed and finished after 30 minutes. Final temperature: 38.
The batch was then moderately agitated for hours at room temperature and an additional 3 hours at 50.
The crude product was dissolved in toluene (300 g.); the solution was quenched on ice. After standing overnight, the aqueous layer was separated in a separatory funnel. The toluene layer was washed once with a 10% sodium bicarbonate solution (200 g.) and then four times with water. It was dried with anhydrous Na SO filtered and freed of the solvent by distillation at a pressure of 60 mm. Toluene recovered (280 g.).
The residual oil was dried for 15 minutes at 50 at a pressure of 2 mm. of mercury. Yield: 143.5 g. of crude ester.
Calcd. Found A.V o 0 S.V. 252 227 Odor: Strong, woody, ambergris.
The NMR shows two ethynyl proton (--CEC H) resonances at 77.36 and 77.42 (3:1 ratio) and two methyl singlets of the acetyl group (CHaE-O) at 77.98 and 77.94 (3:1 ratio).
EXAMPLE XVII l-acetoxy-2-sec-butyl-l-ethynylcyclohexane (cis) (IIIb 2-sec-butyl- 1 -ethynylcyclohexanol (cis) (36 g.) was charged into a 250 ml. fiask fitted with a sealed stirrer, a thermometer, a reflux condenser 'with drying tube and a dropping funnel.
A mixture of acetic anhydride (26 g.) and 85% phosphoric acid (0.3 g.) was added over a period of one hour. The temperature rose from 26 to 33. Agitation was continued for 48 hours. Then, the batch was heated 3 hours at 50. After quenching on ice and neutralization with sodium bicarbonate, the ester was extracted with toluene. The extract was washed three times with water, dried, filtered and freed of the solvent at a pressure of 200 mm.
The residual oil (40.1 g.) was fractionated through a 25" spiral column.
The fraction (14 g.) going over at 97 at a pressure of 1.5 mm. was the desired compound as indicated by IR. NMR had a 1 proton singlet at 77.36 assigned to the ethynyl proton (CEQ H and a 3 proton singlet at 77.98 assigned to the acetoxy methyl Odor: Woody, earthy, musty, ambergris.
EXAMPLE XVIII l-acetoxy-Z-sec-butyl-l-ethynylcyclohexane (trans) (IIIb) Following the procedure for the preceding cis compound in Example XVII but starting with 2-sec-butyl-1- ethynylcyclohexanol (trans, 36 g.), 12.2 g. of the desired ester were obtained. B.P. 97-98, 1.5 mm. IR and NMR are compatible with the indicated structure. The NMR had a 1 proton singlet at 77.42 assigned to the ethynyl proton (CE C I'I and a three proton singlet at 77.94 assigned to the acetoxy methyl H g-O Odor: Strong, woody, vetiveracetate ambergris.
EXAMPLE XIX 2-sec-butyl-l-ethynyl-l-formyloxycyclohexane (IIIb) 16 g) the. agitatedmixture at? 5210 overga period .ofone our.
The batch was agitated 5 hours at 10 and then for 4 /2 days at'roomtemperature. After quenching on ice, the ester was extractedwith petroleum ether..-'1"l1:. ether was washed with sodium carbonate solution and water; the dried and filtered extract was freed of the solvent by distillation. Yield of the crude'ester: 65.9 g.
It was fractionated through a 2 ft.'Goodloefcolumn. The fraction (22.8 g.) going over at 6871 at a pressure of 0.2 mm. was redistilled (micro still), B.P. 721- 74 at 0.3 mm.; yield 17.9 g. I
IR indicates the absence of OH, the presence of czCr-H and HCOO. i NMR is compatible with the assigned structure. I 11 1.4760. Odor: Similar to the acetate, very interesting, woody, ambergris. x VPC: 150. 20 M. Decomposition.
EXAMPLE XX Z-seC-butyI-I-ethynyl-1 propionyloxycyclohexane' (IHb) Z-sec-butyl 1 ethynylcyclohexanol (46.5 g.), toluene ml.) and propionic anhydride (70 g.) were agitated and refluxed 5 hours in a suitable vessel. After quenching on ice, neutralization with sodium bicarbonate, washing the toluene layer with water, drying and filtering, the solvent was removed by distillation at a pressure of 200 mm. The residual oil was fractionated through a 25 spiral column. The fraction which went overat -110 (11.4 g.) at a pressure of 2.4 mm. was the desired ester as indicated by IR analysis. 2
n 1.4707. Odor: Sweet, musty, woody.
EXAMPLE XXI 1-acetoxy-2-sec-butyl-l-vinylcyclohexane (IVb, n= 1) 1-acetoxy-Z-sec-butyl-ethynylcyclohexane 66 g. (mixture cis, trans, about 1:1) dissolved in hexane (20 ml.) Was hydrogenated in a Parr bomb in the presence of Lindlar catalyst (0.25 g.) at 45-50 at a pressure of 45-50 lbs. of hydrogen over a period of 5 /2hours.
Hexane (10 ml.) and Lindlar catalyst (0.75 g.) were added and the hydrogenation was continued underthe above conditions for an additional 3% hours.
Adding of hexane (10 ml.) and of Lindlars catalyst (0.75 g.) was repeated, once, combined,with hydrogenation for 1 /2 hours.
The solution was filtered from the catalyst; the solvent was distilled. The residual oil weighed 65.1 g.
Sixty g. of it were fractionated, using an 18" column filled with glass helices. The fraction (44 g.) going over at 73-79 at a pressure of 0.60.7 mm. was the desired hydrogenation product as indicated by IR'analysis.
Redistillation yielded 31.5 g. of 1-acetoxy'-2sec-butyll-vinylcyclohexane; B.P. 95/1' mm. The structure was confirmed by IR. Th NMR shows three vinyl protons between the 73.5-75.5 region and the ethynyl proton was gone. Two methyl singlets due to the acetoxy 0 (ormbo group at 77.93 and 7.98 show this to he a cis trans mixture.
n =1.4691. Odor: Woody, ambergris. EXAMPLE XXII .i 1-acetoxy-2-sec-butyl-l-ethynylcyclopentane (IIIb, n=0) 27.6 g. 2-sec-butyl-l-ethynylcyclopentanol (.165 m.) was reacted with 17.4' g. acetic anhydride and 0.2 g. 85% phosphoric acid as described in Example XVI to yield 23.9 g. of product; B.P. 84 C. at 1.5mm.
n =l.4660. Odor: Woody, vetiver acetate, cedar.
17 EXAMPLE )OGII 1-acetoxy-2-sec-butyl-l-ethynylcycloheptane (I IIb, n =2) 16.5 g. of 2-sec-butyl-l-ethynylcycloheptanol and 9.5 g. of acetic anhydride and 0.2 ml. 85% phosphoric acid as catalyst were reacted as described in Example XVI.
Yield: 12.3 g. B.P. 118 at 2.5 mm. n =1.4756, Odor: Warm,.woody, note of cedarwood.
EXAMPLE XXIV l-acetoxy-Z-iso-butyl-l-ethynylcyclohexane (IIId) 5.0 g. of crude 2-iso-butyl-l-ethynylcyclohexanol, 3.5 ml. acetic anhydride and 0.1 ml. of 85 phosphoric acid were reacted as described in Example XVI to yield 3.6 g. of product, B.P. 83 C. 0.5 mm.; n =1.4649.
Odor: Warm, woody, tobacco, ambergris.
Y EXAMPLE XXV 1-acetoxy-2-n-butyl-l-ethynylcyclohexane (II'Ia) 6.0 g. of crude 2-n-b'utyl-l-ethynylcyclohexanol, 3.5 ml. acetic anhydride and 0.1 ml. of 85% phosphoric acid were reacted as described in Example XVI to yield 3.6 g. product, B.P. 79' 81 C.0.5 mm.; n =1.4660.
Odor: Woodypspice.
I I EXAMPLE XXVI l-acetoxy-2-sec-butyl-l-ethylcyclohexane (Vb) A mixture of 11.1 g. of 1acetoxy-Z-sec-butyl-l-ethynylcyclohexane, 100 mhmethanol, 1 g. Raney nickel and 0.5 g. soda ash was hydrogenated at 25 C. and 50 p.s.i. to yield 6.0 g. of product, B.P. 94 C. 1.5 mm.; n =1.46l1; IR and NMR show acetate but no OH, Cz-CH,
H -o=on.
Odor: Woody, ambergris.
EXAMPLE XXVII l-acetoxy-2-sec-butyl-1 1-propynyl)cyclohexane (IXb The corresponding propynyl alcohol (19 g.) prepared in Example XIV, acetic anhydride (15 g.) and 85% phosphoric acid (0.16 g.) were brought to reaction and worked up as being described in Example XVI.
The ester had a B.P. of 8590 at a pressure of 0.4 mm, IR indicated complete esterification by lack of OH absorption.
Odor: Woody.
EXAMPLE XXVIII for the methine protons on the carbinol carbon of the two isomers.
A mixture of 312 g. (2.0 mole) of 2-sec-butylcyclohexanol and 2.0 ml. of 93% H 50 was heated to reflux and the Water produced separated in a Dean-Stark tube. After 90 minutes of reflux the water separation slowed down (35 ml. collected) and the reaction mixture was cooled, washed neutral and distilled to yield 231 g. (84% of theory) of sec-butylcyclohexene; B.P. (50 mm) =90 C.; n =1.4588. The mixture contains 3 isomers (A, B, C) in 75:12:13 ratio.
Tert-butyl chromate-To 290 ml. of tert-butanol in a 1 l. flask provided with an agitator and a system for adding solids, a slow addition (under a nitrogen atmosphere) of 100 g. of solid chromic anhydride was initiated. At 10 minutes into the addition the temperature rose from 27 C. to 48 C. and a cooling bath was applied to lower the batch temperature to 28 C. At this point (5 minutes after the cooling bath had been applied) a stopper popped with a flash of light. An additional 5 minutes was required to add the remaining chromate during which time there was no further problems. The reaction mixture was then stirred for another 20 minutes. After adding 500 ml. of dry carbon tetrachloride the reaction mixture was transferred to a separatory funnel using an additional 200 ml. of carbon tetrachloride as washes. The organic layer was filtered through cotton, dried over sodium sulfate, concentrated to 500 ml. at 300 mm. pressure and used subsequently in the following synthetic step.
To the solution of tert-butyl chromate prepared above was added 159 ml. glacial acetic acid and 64 ml. of acetic anhydride. This solution was then added dropwise (over 2.0 hour period while employing a nitrogen atomsphere) to 34.6 grams (.25 mole), of sec-butylcyclohexene at 70 C. The reaction mixture was heated an additional 2 hours at 7075 C., cooled to room temperature and allowed to sit in the dark overnight. A solutionof 102 g. oxalic acid in 1.025 ml. H O was added slowly over a 1.7 hour period while maintaining a temperature of 20-25 C. (some foaming noted). An additional 76.5 g. of solid oxalic acid was added slowly (the first portions caused excessive foaming).
The layers were separated and the aqueous layer extracted with CCl The organic layers were combined and washed with water, 10% sodium bicarbonate, neutral with water, concentrated and distilled to yield 11.7 g. (31% of theory) of 1sec-butylcyclohexen-3-one pure by g.l.c. B.P. (3.0 mm.)=98 C.; n =1.4882; NMR 14.1 (1H) (s).
Hydrogenation of 10 g. of 1sec-butylcyclohexen-3one at room temperature and 40 p.s.i. in a Parr hydrogenator using 0.5 g. 5% Pd/C as catalyst yielded, after distillation on a spinning band column, 4.5 g. of 3-sec-butylcyclohexanone. B.P. (5.0 mm.)=88 C.; n Z=1.4601.
4.6 g. of 3-sec-butylcyclohexanone (.030 mole) was reacted with 3.3 g. lithium acetylide ethylenediamine complex in 7.5 ml. toluene and 7.5 ml..tetrahydrofuran as described in Example I.
After workup the resulting oil was distilled on a Nester/ Faust Auto Annular Teflon spinning band column to yield 0.7 g. of 3-sec-butyl-l-ethynylcyclohexanol, B.P. 105 C. at 5.0 mm., IR showed no carbonyl band and did show the characteristic bands for CECH and OH. Odor: Camphoraceous.
EXAMPLE XXIX 1-acetoxy-3-sec-butyl-l-ethynylcyclohexane 1.8 g. of 3-sec-butyl-l-ethynylcyclohexanol, 1.5 ml. acetic anhydride and 0.02 ml. 85% phosphoric acid were reacted as described previously to yield 1.1 g. of product; B.P. 96-98 C. at 1 mm.; n =1.4679.
Odor: Weak, spicy, peppery.
EXAMPLE XXX 1-acetoxy-2sec-butylcyclohexane A mixture of 39.0 g. 2-sec-butylcyclohexanol, 32 g. of acetic anhydride, and 0.5 g. sodium acetate was refiuxed (136 C.) for 6 hours. After cooling to C., 50 ml. of water were added and the batch refluxed an additional 30 minutes. The batch was cooled to room temperature, diluted with hexane, and the layers separated. The organic layer was washed with 2x 100 ml. water, 2x 50 ml. 5% soda ash, and then neutral with water. Distillation yielded 37.4 grams of product; B.P. 80 C. at 2 mm.
n =l.4503. Odor: Weak, minty.
19 EXAMPLE xxxr 1-acetoxy-2-cyclohexyl-1-ethynylcyclohexane EXAMPLE XXXII 1-ethynyl-2-isopropylcyclohexanol (cis, trans) 2-isopropylcyclohexanone (28.2 g.) in 50 ml. of dry benzene and the lithium acetylide ethylenediamine complex (21 g.) in 200 ml. of dry benzene were brought to reaction and worked up as described in Example I.
The mixture of cis, trans alcohols had a B.P. of 47 at a pressure of 0.8 mm.
Calcd. Found Analysis of CuHiaO:
Percent C 79. 46 79.23 Percent H 10. 92 11. 19
Odor: Camphoraceous.
ECAMPLE )QCXIII Z-tert-butyl-l-ethynylcyclohexanol (cis, trans) (11b) In accordance with the procedure of Example I but using 2-tert-butyl cyclohexanone in place of 2-sec-buty1 cyclohexanone there is obtained Z-tert-butyl-l-ethynylcyclohexanol, B.P. 58/1 mm., 11 1.4831, 99.5% pure by V.P.C., odor: fresh, camphor, woody.
EXAMPLE XXXIV 1-acetoxy-2-tert-butyll-ethynylcyclohexane (cis, trans) (IIIb) In accordance with the procedure of Example XVI 2- tert-butyl-l-ethynylcyclohexanol is reacted with acetic anhydride in the presence of phosphoric acid to yield 1- acetoxy-Z-tert-butyl-l-ethynylcyclohexane, B.P. 85/1 mm., 11, 1.4791, odor: woody, ambergris.
.20 What is claimed is: 1. A compound of the formula wherein R=hydrogen or methyl R"=hydrogen or loweralkanoyl R" =butyl 11:0, 1 or 2 Z is a single, double, or triple bond and b is correspondingly 2, 1 or 0.
2. A compound according to claim 1 wherein R" is acetyl, propionyl or formyl.
3. A compound according to claim 1 wherein n=1, Za triple bond and R" is hydrogen.
1-acetoxy-2-sec-butyl-l-ethynylcyclohexane. 2-sec-butyl-l-ethynylcyclohexanol. Y 1-acetoxy-2-sec-butyl-l-vinylcyclohexane. 2-sec-butyl-l-ethynyl-1-formyloxycyclohexane. 1-acetoxy-2-sec-butyl-l-ethylcyclohexane. 1-acetoxy-2-sec-butyl-l-ethynylcyclohexane (cis). 10. 2-sec-butyl-l-ethynylcyclohexanol (cis). 11. 2-sec-butyl-1-ethynylcyclohexanol (trans). 12. l-acetoxy-Z-sec-butyl-l-ethynylcyclohexane (trans).
References Cited I UNITED STATES PATENTS I 8/1938 Macallum 260-638 2,125,384 3,153,097 10/1964 Cameron 260-638 3,225,110 12/1965 Kurtz 260638 OTHER REFERENCES VIVIAN GARNER, Primary Examiner US. 01. X.R. I 252-522; 260-491, 586 R, 617 E, 617 M, 617 R, 631 R UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,7 9,55 Dated October l9" It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
I Col-:1, Llne 2: No hyphen cycles.
be'ween alkerzyl and .-:en. (fralkynylcycloalkano) l Col- '-l', Lane 13: Correct "2- butyl" to "Z-Butvl", also l-alkynylcycloalkan.
'30}- 2, Line 19: Correct 2-b I utyl cycloalkanone to 2-.:'.::ylcycloalkanone.
hart:
, Formula (VI) must be corrected to:
H=CH
RI2I ORM PO-IOSO (10-69) U SCOMM-DC 60376-F'69 ,5 GOVERNMENT PRINTING OFFICE: 8 69. o
UNITED STATES PATENT OFF ICE P g 2 CERTIFICATE OF CORRECTION Patent: No. $769,330 Dated ectober 30 197,
Inventor(s) Edward J. Nikawikz, at 81.
It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Formula (IV) must be corrected to:
R o Y CH=CH2 I R! I I extend arrow Line 62. Correct to l- -ethynylcycloalkan V 3g "Aniber ris I "amberg i Y 9 1.5 preferred t A Line 62: Correct to "Minutes".
Line 19: Correct to butyl-l-ethynylcyclo--= 5 sic-fl d 11316 El, insert Table as a we "F r ORM PO-105O I 10-69) USCOMM-DC 60376-P69 [1.5 GOVERNMENT PRINTING OFFICE:
UNITED STATES PATENT OFFICE Page 5 CERTIFICATE 0F CORECTIGN Patent No. 3 769 530 Dated OCCODQI" 30, 1975 Inventor s Edward J. Nikawitz et a1.
It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
L Lines 42, 43: Correction;- the whole 15 scrambled up. The cologne without l-acetoxy-2-secbutyll-ethynylcyclo-hexane is thin and not as pleasing, The richness and balance contributed by l-acetoxy-Z -sec-hutyl-l-ethynylcyclohexane in this case is outstanding.
Col 9, Line 3?: Correct to 'r 7.4 7060 1.19, Line 48: Correct to "dry ice condenser".
COL Line 43: Correct to "2-isobutylcyclohexan one." I
Col. 1L, Line 12: Correct to "distilled".
....(ol@ l7 :line ll,- Correct to Line 12'. 2-isobutyL-l- .4
Signed and sealed this 17th day of June 1975,
(SEAL) Attest:
' C. MARSHALL DANN RUTH G. MASUN Commissioner of Patents Attesting Officer and Trademarks FORM PC4050 (IO-69) USCOMM- e037 -p69 u.s GOVERNMENT rmm'mo omcz: 569 93 Q
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3984354A (en) * 1971-12-27 1976-10-05 Monsanto Company 1-(3'-Hexenyl)-1-cycloalkanols and their esters
US4088681A (en) * 1975-12-27 1978-05-09 Basf Aktiengesellschaft Substituted 1-alkenynyl-cyclohexanols and -cyclohexenes and processes for their preparation
US4277618A (en) * 1977-12-12 1981-07-07 Givaudan Corporation 2-Substituted-1-acetoxy and hydroxy-1-methyl-cyclohexanes
WO1998047842A1 (en) * 1997-04-23 1998-10-29 Quest International B.V. Perfumes comprising 3-alkylcycloalkanols
US20150159118A1 (en) * 2013-12-11 2015-06-11 International Flavors & Fragrances Inc. Novel cyclopentanol compounds

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5947936A (en) * 1982-09-10 1984-03-17 株式会社東芝 Load controller of combined cycle turbine plant
DE3609524A1 (en) * 1986-03-21 1987-09-24 Henkel Kgaa ISOMERE 1-ALKYL / ALKENYL-2,2,4 (2,4,4) -TRIMETHYL-CYCLOPENTAN-1-OLE AS A FRAGRANCE
WO2009033096A2 (en) 2007-09-07 2009-03-12 Avery Dennison Corporation Block out label, label sheet, and related method
US8436005B2 (en) 2008-04-03 2013-05-07 Abbott Laboratories Macrocyclic pyrimidine derivatives
FR2996551B1 (en) * 2012-10-05 2015-01-09 Mane Fils V PROCESS FOR THE SYNTHESIS OF CYCLOHEXENONES AND THEIR USE IN PERFUMERY
EP3640234A1 (en) 2018-10-16 2020-04-22 Basf Se Ethers and esters of 1-substituted cycloalkanols for use as aroma chemicals

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1617009A1 (en) * 1966-05-20 1971-02-11 Int Flavors & Fragrances Inc Fragrances

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3984354A (en) * 1971-12-27 1976-10-05 Monsanto Company 1-(3'-Hexenyl)-1-cycloalkanols and their esters
US4088681A (en) * 1975-12-27 1978-05-09 Basf Aktiengesellschaft Substituted 1-alkenynyl-cyclohexanols and -cyclohexenes and processes for their preparation
US4277618A (en) * 1977-12-12 1981-07-07 Givaudan Corporation 2-Substituted-1-acetoxy and hydroxy-1-methyl-cyclohexanes
WO1998047842A1 (en) * 1997-04-23 1998-10-29 Quest International B.V. Perfumes comprising 3-alkylcycloalkanols
US6313087B1 (en) 1997-04-23 2001-11-06 Quest International Bv Perfumes comprising 3-alkylcycloalkanols
US20150159118A1 (en) * 2013-12-11 2015-06-11 International Flavors & Fragrances Inc. Novel cyclopentanol compounds
US9290718B2 (en) * 2013-12-11 2016-03-22 International Flavors & Fragrances Inc. Cyclopentanol compounds
US20160160152A1 (en) * 2013-12-11 2016-06-09 International Flavors & Fragrances Inc. Novel cyclopentanol compounds
US9701925B2 (en) * 2013-12-11 2017-07-11 International Flavors & Fragrances Inc. Cyclopentanol compounds

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CH575757A5 (en) 1976-05-31
DE2155671C3 (en) 1981-12-03
DE2155671A1 (en) 1972-05-18
FR2113740A5 (en) 1972-06-23
BR7107487D0 (en) 1973-06-14
TR16913A (en) 1973-09-01
NL161126B (en) 1979-08-15
NL7115452A (en) 1972-05-15
CA996135A (en) 1976-08-31
ES396810A1 (en) 1974-06-01
JPS5126430B1 (en) 1976-08-06
DE2155671B2 (en) 1981-01-08
ZA717114B (en) 1972-07-26
JPS51110047A (en) 1976-09-29
JPS5417010B2 (en) 1979-06-27
SU422134A3 (en) 1974-03-30
SE385117B (en) 1976-06-08
IT951597B (en) 1973-07-10
CH568950A5 (en) 1975-11-14
AU3556571A (en) 1973-05-17
NL161126C (en) 1980-01-15
GB1344653A (en) 1974-01-23
BE775152A (en) 1972-05-10

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